OBJECTIVES: The purpose of this study was to identify sex-specific outcomes of intermediate risk patients undergoing transcatheter aortic valve replacement with the SAPIEN 3 valve. BACKGROUND: A survival difference has been observed in women as compared with men in inoperable and high-risk patients receiving early-generation balloon-expandable valves for transcatheter aortic valve replacement (TAVR). Whether a sex-specific outcome difference persists with newer-generation valves and in lower-risk patients is unknown. METHODS: The PARTNER (Placement of Aortic Transcatheter Valves) II S3 trial included high-risk (HR) (Society of Thoracic Surgeons risk score >8% or heart team determination) and intermediate-risk (IR) (Society of Thoracic Surgeons risk score 4% to 8% or heart team determination) patients with severe symptomatic aortic stenosis who were treated with TAVR with the SAPIEN 3 valve. Patient characteristics and clinical outcomes at 30 days and 1 year were compared by sex. RESULTS: Between October 2013 and December 2014, 1,661 patients were enrolled: 583 were HR (338 men, 245 women) and 1,078 were IR (666 men, 412 women). In both cohorts, women were more likely than men to be frail (22% vs. 13%; p < 0.001), but less likely to have comorbid conditions of renal insufficiency, coronary artery disease, atrial fibrillation, or chronic obstructive pulmonary disease. Women were more likely to receive ≤23-mm valves (74.1% vs. 11.1%; p < 0.001) and were less likely to receive 29-mm valves (1.4% vs. 35.1%; p < 0.001). In the combined cohorts, there was no difference in mortality for women compared with men at 30 days (2.0% vs. 1.2%; p = 0.20) or 1 year (9.3% vs. 10.2%; p = 0.59). There were no differences in disabling stroke or any stroke at 30 days or 1 year; however, women had an increased rate of minor stroke at 30 days (2.1% vs. 0.7%; p = 0.01). Female sex was associated with increased major vascular complications (7.9% vs. 4.4%; p = 0.003), but not with moderate or severe paravalvular regurgitation. Notably, similar outcomes regarding sex-specific outcomes were obtained within stratified analyses of the HR and IR cohorts. CONCLUSIONS: The study found no apparent sex-specific differences in survival or stroke in this trial of TAVR. This may reflect the changing demographic of patients enrolled, use of newer-generation valves with more sizes available, and more accurate valve sizing techniques.